Predictors of tumour dynamics over a 6-week course of concurrent chemoradiotherapy for glioblastoma and the impact on survival.

PURPOSE: We present the final analyses of tumour dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy (chemoRT) for glioblastoma (GBM) in the GLIO study. METHODS AND MATERIALS: This is a prospective serial MR imaging study in 129 patients with GBM who had MRIs obtained at RT planning (F0), fraction-10 (F10), fraction-20 (F20), and 1-month post-RT. Tumour dynamics assessed included gross tumour volume (GTV) relative to F0 (Vrel), and tumour migration distance (dmigration). Covariables evaluated included: corpus callosum involvement, extent of surgery, MGMT methylation and IDH mutation status. RESULTS: The median Vrel were 0.85 (range: 0.25-2.29) at F10, 0.79 (range: 0.09-2.22) at F20 and 0.78 (range: 0.13-4.27) at P1M. The median dmigration were 4.7mm (range: 1.1-20.4mm) at F10, 4.7mm (range: 0.8-20.7mm) at F20 and 6.1mm (range: 0.0-45.5mm) at P1M. Compared to patients who had corpus callosum involvement (n=26), those without corpus callosum involvement (n=103) had significant Vrel reduction at F20 (P=0.03) and smaller dmigration at F20 (P=0.007). Compared to patients who had biopsy alone (n=19) and subtotal resection (n=71), those who had gross total resection (n=38) had significant Vrel reduction at F10 (P=0.001) and F20 (P=0.001) and a smaller dmigration at F10 (P=0.03) and F20 (P=0.002). MGMT methylation and IDH mutation status were not significantly associated with tumour dynamics. The median progression free survival and overall survival (OS) were 8.5 months (95%CI=6.9-9.9) and 20.4 months (95%CI=17.6-25.2). In multivariable analyses, patients with Vrel≥1.33 at F10 had worse OS (HR=4.6; 95%CI=1.8-11.4; P=0.001), while patients with dmigration≥5mm at 1-month post-RT had worse PFS (HR=1.76; 95%CI=1.08-2.87) and OS (HR=2.2; 95%CI=1.2-4.0; P=0.007). CONCLUSION: Corpus callosum involvement and extent of surgery are independent predictors of tumour dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumour enlargement at F10 and tumour migration 1-month post-RT were associated with poorer OS.

Utility of molecular markers in predicting local control specific to lung cancer spine metastases treated with stereotactic body radiotherapy.

BACKGROUND AND PURPOSE: We report outcomes following spine stereotactic body radiotherapy (SBRT) in metastatic non-small cell lung cancer (NSCLC) and the significance of programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR) mutation and timing of immune check point inhibitors (ICI) on local failure (LF). MATERIALS AND METHODS: 165 patients and 389 spinal segments were retrospectively reviewed from 2009 to 2021. Baseline patient characteristics, treatment and outcomes were abstracted. Primary endpoint was LF and secondary, overall survival (OS) and vertebral compression fracture (VCF). Multivariable analysis (MVA) evaluated factors predictive of LF and VCF. RESULTS: The median follow-up and OS were: 13.0 months (range, 0.5-95.3 months) and 18.4 months (95% CI 11.4-24.6). 52.1% were male and 76.4% had adenocarcinoma. Of the 389 segments, 30.3% harboured an EGFR mutation and 17.0% were PD-L1 ≥ 50%. The 24 months LF rate in PD-L1 ≥ 50% vs PD-L1 < 50% was 10.7% vs. 38.0%, and in EGFR-positive vs. negative was 18.1% vs. 30.0%. On MVA, PD-L1 status of ≥ 50% (HR 0.32, 95% CI 0.15-0.69, p = 0.004) significantly predicted for lower LF compared to PD-L1 < 50%. Lower LF trend was seen with ICI administration peri and post SBRT (HR 0.41, 95% CI 0.16-1.05, p = 0.062). On MVA, polymetastatic disease (HR 3.28, 95% CI 1.84-5.85, p < 0.0001) and ECOG ≥ 2 (HR 1.87, 95% CI 1.16-3.02, p = 0.011) significantly predicted for worse OS and absence of baseline VCF predicted for lower VCF rate (HR 0.20, 95% CI 0.10-0.39, p < 0.0001). CONCLUSION: We report a significant association of PD-L1 ≥ 50% status on improved LC rates from spine SBRT in NSCLC patients.

Evolving concepts in margin strategies and adaptive radiotherapy for glioblastoma: A new future is on the horizon.

Chemoradiotherapy is the standard treatment after maximal safe resection for glioblastoma (GBM). Despite advances in molecular profiling, surgical techniques, and neuro-imaging, there have been no major breakthroughs in radiotherapy (RT) volumes in decades. Although the majority of recurrences occur within the original gross tumor volume (GTV), treatment of a clinical target volume (CTV) ranging from 1.5 to 3.0 cm beyond the GTV remains the standard of care. Over the past 15 years, the incorporation of standard and functional MRI sequences into the treatment workflow has become a routine practice with increasing adoption of MR simulators, and new integrated MR-Linac technologies allowing for daily pre-, intra- and post-treatment MR imaging. There is now unprecedented ability to understand the tumor dynamics and biology of GBM during RT, and safe CTV margin reduction is being investigated with the goal of improving the therapeutic ratio. The purpose of this review is to discuss margin strategies and the potential for adaptive RT for GBM, with a focus on the challenges and opportunities associated with both online and offline adaptive workflows. Lastly, opportunities to biologically guide adaptive RT using non-invasive imaging biomarkers and the potential to define appropriate volumes for dose modification will be discussed.

Stereotactic body radiation therapy for spinal metastases: A new standard of care.

Advancements in systemic therapies for patients with metastatic cancer have improved overall survival and, hence, the number of patients living with spinal metastases. As a result, the need for more versatile and personalized treatments for spinal metastases to optimize long-term pain and local control has become increasingly important. Stereotactic body radiation therapy (SBRT) has been developed to meet this need by providing precise and conformal delivery of ablative high-dose-per-fraction radiation in few fractions while minimizing risk of toxicity. Additionally, advances in minimally invasive surgical techniques have also greatly improved care for patients with epidural disease and/or unstable spines, which may then be combined with SBRT for durable local control. In this review, we highlight the indications and controversies of SBRT along with new surgical techniques for the treatment of spinal metastases.

Brain Tumor Imaging in Adolescents and Young Adults: 2021 WHO Updates for Molecular-based Tumor Types.

Published in 2021, the fifth edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) introduced new molecular criteria for tumor types that commonly occur in either pediatric or adult age groups. Adolescents and young adults (AYAs) are at the intersection of adult and pediatric care, and both pediatric-type and adult-type CNS tumors occur at that age. Mortality rates for AYAs with CNS tumors have increased by 0.6% per year for males and 1% per year for females from 2007 to 2016. To best serve patients, it is crucial that both pediatric and adult radiologists who interpret neuroimages are familiar with the various pediatric- and adult-type brain tumors and their typical imaging morphologic characteristics. Gliomas account for approximately 80% of all malignant CNS tumors in the AYA age group, with the most common types observed being diffuse astrocytic and glioneuronal tumors. Ependymomas and medulloblastomas also occur in the AYA population but are seen less frequently. Importantly, biologic behavior and progression of distinct molecular subgroups of brain tumors differ across ages. This review discusses newly added or revised gliomas in the fifth edition of the CNS WHO classification, as well as other CNS tumor types common in the AYA population.

Stereotactic Body Radiation Therapy for Sacral Metastases: Deviation From Recommended Target Volume Delineation Increases the Risk of Local Failure.

PURPOSE: Although spine stereotactic body radiation therapy (SBRT) is considered a standard of care in the mobile spine, mature evidence reporting outcomes specific to sacral metastases is lacking. Furthermore, there is a need to validate the existing sacral SBRT international consensus contouring guidelines to define the optimal contouring approach. We report mature rates of local failure (LF), adverse events, and the effect of contouring deviations in the largest experience to date specific to sacrum SBRT. METHODS AND MATERIALS: Consecutive patients who underwent sacral SBRT from 2010 to 2021 were retrospectively reviewed. The primary endpoint was magnetic resonance imaging-based LF with a focus on adherence to target volume contouring recommendations. Secondary endpoints included vertebral compression fracture and neural toxicity. RESULTS: Of the 215 sacrum segments treated in 112 patients, most received 30 Gy/4 fractions (51%), 24 Gy/2 fractions (31%), or 30 Gy/5 fractions (10%). Sixteen percent of segments were nonadherent to the consensus guideline with a more restricted target volume (undercontoured). The median follow-up was 21.4 months (range, 1.5-116.9 months). The cumulative incidence of LF at 1 and 2 years was 18.4% and 23.1%, respectively. In those with guideline adherent versus nonadherent contours, the LF rate at 1 year was 15.1% versus 31.4% and at 2 years 18.8% versus 40.0% (hazard ratio [HR], 2.5; 95% CI, 1.4-4.6; P = .003), respectively. On multivariable analysis, guideline nonadherence (HR, 2.4; 95% CI, 1.3-4.7; P = .008), radioresistant histology (HR, 2.4; 95% CI, 1.4-4.1; P < .001), and extraosseous extension (HR, 2.5; 95% CI, 1.3-4.7; P = .005) predicted for an increased risk of LF. The cumulative incidence of vertebral compression fracture was 7.1% at 1 year and 12.3% at 2 years. Seven patients (6.3%) developed peripheral nerve toxicity, of whom 4 had been previously radiated. CONCLUSIONS: Sacral SBRT is associated with high efficacy rates and an acceptable toxicity profile. Adhering to consensus guidelines for target volume delineation is recommended to reduce the risk of LF.

Magnetic Resonance Imaging Frequency After Stereotactic Body Radiation Therapy for Spine Metastases.

PURPOSE: Stereotactic body radiation therapy (SBRT) is increasingly being used to treat spine metastases. Current post-SBRT imaging surveillance strategies in this patient population may benefit from a more data-driven and personalized approach. The objective of this study was to develop risk-stratified post-SBRT magnetic resonance imaging (MRI) surveillance strategies using quantitative methods. METHODS AND MATERIALS: Adult patients with bony spine metastases treated with SBRT between 2008 and 2021 and who had at least 2 follow-up spine MRIs were reviewed retrospectively. A recursive partitioning analysis model was developed to separate patients into different risk categories for post-SBRT progression anywhere within the spine. Imaging intervals were derived for each risk category using parametric survival regression based on multiple expected spine progression rates per scan. RESULTS: A total of 446 patients and 1039 vertebral segments were included. Cumulative incidence of spine progression was 19.2% at 1 year, 26.7% at 2 years, and 35.3% at 4 years. The internally validated risk stratification model was able to divide patients into 3 risk categories based on epidural disease, paraspinal disease, and Spinal Instability Neoplastic Score category. The 4-year risk of spine progression was 23.4%, 39.0%, and 51.8%, respectively, for the low-, intermediate-, and high-risk groups. Using an expected per-scan spine progression rate of 3.75%, the low-risk group would require follow-up scans every 6.0 months (95% CI, 4.9-7.6) and the intermediate-risk group would require surveillance every 3.1 months (95% CI, 2.6-3.7). At an expected spine progression rate of 5%, the high-risk group would require surveillance every 1.3 months (95% CI, 1.1-1.6) during the first 13.2 months after SBRT and every 5.9 months thereafter (95% CI, 2.8-12.3). CONCLUSIONS: Data-driven follow-up MRI surveillance intervals at a range of expected spine progression rates have been determined for patients at different risks of spine progression based on an internally validated, single-institution risk stratification model.

Practice and principles of stereotactic body radiation therapy for spine and non-spine bone metastases.

Radiotherapy is the dominant treatment modality for painful spine and non-spine bone metastases (NSBM). Historically, this was achieved with conventional low dose external beam radiotherapy, however, stereotactic body radiotherapy (SBRT) is increasingly applied for these indications. Meta-analyses and randomized clinical trials have demonstrated improved pain response and more durable tumor control with SBRT for spine metastases. However, in the setting of NSBM, there is limited evidence supporting global adoption and large scale randomized clinical trials are in need. SBRT is technically demanding requiring careful consideration of organ at risk tolerance, and strict adherence to technical requirements including immobilization, simulation, contouring and image-guidance procedures. Additional considerations include follow up practices after SBRT, with appropriate imaging playing a critical role in response assessment. Finally, there is renewed research into promising new technologies that may further refine the use of SBRT in both spinal and NSBM in the years to come.

Dose-Escalated Radiation Therapy Is Associated With Improved Outcomes for High-Grade Meningioma.

PURPOSE: The optimal modern radiation therapy (RT) approach after surgery for atypical and malignant meningioma is unclear. We present results of dose escalation in a single-institution cohort spanning 2000 to 2021. METHODS AND MATERIALS: Consecutive patients with histopathologic grade 2 or 3 meningioma treated with RT were reviewed. A dose-escalation cohort (≥66 Gy equivalent dose in 2-Gy fractions using an α/ß = 10) was compared with a standard-dose cohort (<66 Gy). Outcomes were progression-free survival (PFS), cause-specific survival, overall survival (OS), local failure (LF), and radiation necrosis. RESULTS: One hundred eighteen patients (111 grade 2, 94.1%) were identified; 54 (45.8%) received dose escalation and 64 (54.2%) standard dose. Median follow-up was 45.4 months (IQR, 24.0-80.0 months) and median OS was 9.7 years (Q1: 4.6 years, Q3: not reached). All dose-escalated patients had residual disease versus 65.6% in the standard-dose cohort (P < .001). PFS at 3, 4, and 5 years in the dose-escalated versus standard-dose cohort was 78.9%, 72.2%, and 64.6% versus 57.2%, 49.1%, and 40.8%, respectively, (P = .030). On multivariable analysis, dose escalation (hazard ratio [HR], 0.544; P = .042) was associated with improved PFS, whereas ≥2 surgeries (HR, 1.989; P = .035) and older age (HR, 1.035; P < .001) were associated with worse PFS. The cumulative risk of LF was reduced with dose escalation (P = .016). Multivariable analysis confirmed that dose escalation was protective for LF (HR, 0.483; P = .019), whereas ≥2 surgeries before RT predicted for LF (HR, 2.145; P = .008). A trend was observed for improved cause-specific survival and OS in the dose-escalation cohort (P < .1). Seven patients (5.9%) developed symptomatic radiation necrosis with no significant difference between the 2 cohorts. CONCLUSIONS: Dose-escalated RT with ≥66 Gy for high-grade meningioma is associated with improved local control and PFS with an acceptable risk of radiation necrosis.

Tumor volumes in T3 supraglottic cancers treated with radiotherapy in the modern era: A study of the Canadian Head & Neck Collaborative Research Initiative.

PURPOSE: To evaluate the association of primary tumor volume (TV) with overall survival (OS) and disease-free survival (DFS) in T3 N0-3M0 supraglottic cancers treated with intensity-modulated radiotherapy (IMRT). METHODS: This was a retrospective cohort study involving 239 patients diagnosed with T3 N0-3M0 supraglottic cancers between 2002 and 2018 from seven regional cancer centers in Canada. Clinical data were obtained from the patient records. Supraglottic TV was measured by neuroradiologists on diagnostic imaging. Kaplan-Meier method was used for survival probabilities, and a restricted cubic spline Cox proportional hazards regression analysis was used to analyze TV associations with OS and DFS. RESULTS: Mean (SD) of participants was 65.2 (9.4) years; 176 (73.6%) participants were male. 90 (38%) were N0, and 151 (64%) received concurrent systemic therapy. Mean TV (SD) was 11.37 (12.11) cm3 . With mean follow up (SD) of 3.28 (2.60) years, 2-year OS was 72.7% (95% CI 66.9%-78.9%) and DFS was 53.6% (47.4%-60.6%). Increasing TV was associated (per cm3 increase) with worse OS (HR, 1.01, 95% CI 1.00-1.02, p < 0.01) and DFS (HR, 1.01, 95% CI 1.00-1.02, p = 0.02). CONCLUSIONS: Increasing primary tumor volume is associated with worse OS and DFS in T3 supraglottic cancers treated with IMRT, with no clear threshold. The findings suggest that patients with larger tumors and poor baseline laryngeal function may benefit from upfront laryngectomy with adjuvant radiotherapy.

Brain Age Estimation on a Dementia Cohort Using FLAIR MRI Biomarkers.

BACKGROUND AND PURPOSE: The prodromal stage of Alzheimer's disease presents an imperative intervention window. This work focuses on using brain age prediction models and biomarkers from FLAIR MR imaging to identify subjects who progress to Alzheimer's disease (converting mild cognitive impairment) or those who remain stable (stable mild cognitive impairment). MATERIALS AND METHODS: A machine learning model was trained to predict the age of normal control subjects on the basis of volume, intensity, and texture features from 3239 FLAIR MRI volumes. The brain age gap estimation (BrainAGE) was computed as the difference between the predicted and true age, and it was used as a biomarker for both cross-sectional and longitudinal analyses. Differences in biomarker means, slopes, and intercepts were investigated using ANOVA and Tukey post hoc test. Correlation analysis was performed between brain age gap estimation and established Alzheimer's disease indicators. RESULTS: The brain age prediction model showed accurate results (mean absolute error = 2.46 years) when testing on held out normal control data. The computed BrainAGE metric showed significant differences between the stable mild cognitive impairment and converting mild cognitive impairment groups in cross-sectional and longitudinal analyses, most notably showing significant differences up to 4 years before conversion to Alzheimer's disease. A significant correlation was found between BrainAGE and previously established Alzheimer's disease conversion biomarkers. CONCLUSIONS: The BrainAGE metric can allow clinicians to consider a single explainable value that summarizes all the biomarkers because it considers many dimensions of disease and can determine whether the subject has normal aging patterns or if he or she is trending into a high-risk category using a single value.

Detecting conversion from mild cognitive impairment to Alzheimer's disease using FLAIR MRI biomarkers.

Mild cognitive impairment (MCI) is the prodromal phase of Alzheimer's disease (AD) and while it presents as an imperative intervention window, it is difficult to detect which subjects convert to AD (cMCI) and which ones remain stable (sMCI). The objective of this work was to investigate fluid-attenuated inversion recovery (FLAIR) MRI biomarkers and their ability to differentiate between sMCI and cMCI subjects in cross-sectional and longitudinal data. Three types of biomarkers were investigated: volume, intensity and texture. Volume biomarkers included total brain volume, cerebrospinal fluid volume (CSF), lateral ventricular volume, white matter lesion volume, subarachnoid CSF, and grey matter (GM) and white matter (WM), all normalized to intracranial volume. The mean intensity, kurtosis, and skewness of the GM and WM made up the intensity features. Texture features quantified homogeneity and microstructural tissue changes of GM and WM regions. Composite indices were also considered, which are biomarkers that represent an aggregate sum (z-score normalization and summation) of all biomarkers. The FLAIR MRI biomarkers successfully identified high-risk subjects as significant differences (p < 0.05) were found between the means of the sMCI and cMCI groups and the rate of change over time for several individual biomarkers as well as the composite indices for both cross-sectional and longitudinal analyses. Classification accuracy and feature importance analysis showed volume biomarkers to be most predictive, however, best performance was obtained when complimenting the volume biomarkers with the intensity and texture features. Using all the biomarkers, accuracy of 86.2 % and 69.2 % was achieved for normal control-AD and sMCI-cMCI classification respectively. Survival analysis demonstrated that the majority of the biomarkers showed a noticeable impact on the AD conversion probability 4 years prior to conversion. Composite indices were the top performers for all analyses including feature importance, classification, and survival analysis. This demonstrated their ability to summarize various dimensions of disease into single-valued metrics. Significant correlation (p < 0.05) with phosphorylated-tau and amyloid-beta CSF biomarkers was found with all the FLAIR biomarkers. The proposed biomarker system is easily attained as FLAIR is routinely acquired, models are not computationally intensive and the results are explainable, thus making this pipeline easily integrated into clinical workflow.

Chemical Exchange Saturation Transfer MRI: What Neuro-Oncology Clinicians Need To Know.

Chemical exchange saturation transfer (CEST) is a relatively novel magnetic resonance imaging (MRI) technique with an image contrast designed for in vivo measurement of certain endogenous molecules with protons that are exchangeable with water protons, such as amide proton transfer commonly used for neuro-oncology applications. Recent technological advances have made it feasible to implement CEST on clinical grade scanners within practical acquisition times, creating new opportunities to integrate CEST in clinical workflow. In addition, the majority of CEST applications used in neuro-oncology are performed without the use gadolinium-based contrast agents which are another appealing feature of this technique. This review is written for clinicians involved in neuro-oncologic care (nonphysicists) as the target audience explaining what they need to know as CEST makes its way into practice. The purpose of this article is to (1) review the basic physics and technical principles of CEST MRI, and (2) review the practical applications of CEST in neuro-oncology.

Relationship between apparent diffusion coefficient and survival as a function of distance from gross tumor volume on radiation planning MRI in newly diagnosed glioblastoma.

PURPOSE: To investigate the changes in apparent diffusion coefficient (ADC) within incrementally-increased margins beyond the gross tumor volume (GTV) on post-operative radiation planning MRI and their prognostic utility in glioblastoma. METHODS: Radiation planning MRIs of adult patients with newly diagnosed glioblastoma from 2017 to 2020 were assessed. The ADC values were normalized to contralateral normal white matter (nADC). Using 1 mm isotropic incremental margin increases from the GTV, the nADC values were calculated at each increment. Age, ECOG performance status, extent of resection and MGMT promoter methylation status were obtained from medical records. Using univariate and multivariable Cox regression analysis, association of nADC to progression-free and overall survival (PFS, OS) was assessed at each increment. RESULTS: Seventy consecutive patients with mean age of 53.6 ± 10.3 years, were evaluated. The MGMT promoter was methylated in 31 (44.3%), unmethylated in 36 (51.6%) and unknown in 3 (4.3%) patients. 11 (16%) underwent biopsy, 41 (44%) subtotal resection and 18 (26%) gross total resection. For each 1 mm increase in distance from GTV, the nADC decreased by 0.16% (p < 0.0001). At 1-5 mm increment, the nADC was associated with OS (p < 0.01). From 6 to 11 mm increment the nADC was associated with OS with the p-value gradually increasing from 0.018 to 0.046. nADC was not associated with PFS. CONCLUSION: The nADC values at 1-11 mm increments from the GTV margin were associated with OS. Future prospective multicenter studies are needed to validate the findings and to pave the way for the utilization of ADC for margin reduction in radiation planning.

Segmentation of Brain Metastases Using Background Layer Statistics (BLAST).

BACKGROUND AND PURPOSE: Accurate segmentation of brain metastases is important for treatment planning and evaluating response. The aim of this study was to assess the performance of a semiautomated algorithm for brain metastases segmentation using Background Layer Statistics (BLAST). MATERIALS AND METHODS: Nineteen patients with 48 parenchymal and dural brain metastases were included. Segmentation was performed by 4 neuroradiologists and 1 radiation oncologist. K-means clustering was used to identify normal gray and white matter (background layer) in a 2D parameter space of signal intensities from postcontrast T2 FLAIR and T1 MPRAGE sequences. The background layer was subtracted and operator-defined thresholds were applied in parameter space to segment brain metastases. The remaining voxels were back-projected to visualize segmentations in image space and evaluated by the operators. Segmentation performance was measured by calculating the Dice-Sørensen coefficient and Hausdorff distance using ground truth segmentations made by the investigators. Contours derived from the segmentations were evaluated for clinical acceptance using a 5-point Likert scale. RESULTS: The median Dice-Sørensen coefficient was 0.82 for all brain metastases and 0.9 for brain metastases of ≥10 mm. The median Hausdorff distance was 1.4 mm. Excellent interreader agreement for brain metastases volumes was found with an intraclass correlation coefficient = 0.9978. The median segmentation time was 2.8 minutes/metastasis. Forty-five contours (94%) had a Likert score of 4 or 5, indicating that the contours were acceptable for treatment, requiring no changes or minor edits. CONCLUSIONS: We show accurate and reproducible segmentation of brain metastases using BLAST and demonstrate its potential as a tool for radiation planning and evaluating treatment response.

Safety of Magnetic Resonance Imaging in Pregnancy.

Magnetic resonance imaging is being increasingly used to diagnose and follow up a variety of medical conditions in pregnancy, both for maternal and fetal indications. However, limited data regarding its safe use in pregnancy may be a source of anxiety and avoidance for both patients and their healthcare providers. In this review, we critically discuss the main safety concerns of Magnetic Resonance Imaging (MRI) in pregnancy including energy deposition, acoustic noise, and use of contrast agents, supported by data from animal and human studies. Use of maternal sedatives and concerns related to occupational exposure in pregnant personnel are also addressed. Exposure to gadolinium-based contrast agents and sedation for MRI during pregnancy should be avoided whenever feasible.

Diffusion-weighted imaging on an MRI-linear accelerator to identify adversely prognostic tumour regions in glioblastoma during chemoradiation.

BACKGROUND AND PURPOSE: Survival in glioblastoma might be extended by escalating the radiotherapy dose to treatment-resistant tumour and adapting to tumour changes. Diffusion-weighted imaging (DWI) on MRI-linear accelerators (MR-Linacs) could be used to identify a dose escalation target, but its prognostic value must be demonstrated. The purpose of this study was to determine whether MR-Linac DWI can assess treatment response in glioblastoma and whether changes in DWI show greater prognostic value than changes in the contrast-enhancing gross tumour volume (GTV). MATERIALS AND METHODS: Seventy-five patients with glioblastoma were treated with chemoradiotherapy, of which 32 were treated on a 1.5 T MRI-linear accelerator (MR-Linac). Patients were imaged with simulation MRI scanners (MR-sim) at treatment planning and weeks 2, 4, and 10 after treatment start. Twenty-eight patients had additional MR-Linac DWI sequences. Cox modelling was used to evaluate the correlation of overall and progression-free survival (OS and PFS) with clinical variables and volumetric changes in the GTV and low-ADC regions (ADC < 1.25 µm2/ms within GTV). RESULTS: In total, 479 MR-Linac DWI and 289 MR-sim DWI datasets were analyzed. MR-Linac low-ADC changes between weeks 2 and 5 inclusive were prognostic for OS (hazard ratio lower limits ≥ 1.2, p-values ≤ 0.02). MR-sim low-ADC changes showed greater correlation with OS and PFS than GTV changes (e.g., OS hazard ratio at week 2 was 3.4 (p <0.001) for low-ADC versus 2.0 (p = 0.022) for GTV). CONCLUSION: MR-Linac DWI can measure low-ADC tumour volumes that correlate with OS and PFS better than contrast-enhancing GTV. Low-ADC regions could serve as dose escalation targets.

Synthesis of diffusion-weighted MRI scalar maps from FLAIR volumes using generative adversarial networks.

Introduction: Acquisition and pre-processing pipelines for diffusion-weighted imaging (DWI) volumes are resource- and time-consuming. Generating synthetic DWI scalar maps from commonly acquired brain MRI sequences such as fluid-attenuated inversion recovery (FLAIR) could be useful for supplementing datasets. In this work we design and compare GAN-based image translation models for generating DWI scalar maps from FLAIR MRI for the first time. Methods: We evaluate a pix2pix model, two modified CycleGANs using paired and unpaired data, and a convolutional autoencoder in synthesizing DWI fractional anisotropy (FA) and mean diffusivity (MD) from whole FLAIR volumes. In total, 420 FLAIR and DWI volumes (11,957 images) from multi-center dementia and vascular disease cohorts were used for training/testing. Generated images were evaluated using two groups of metrics: (1) human perception metrics including peak signal-to-noise ratio (PSNR) and structural similarity (SSIM), (2) structural metrics including a newly proposed histogram similarity (Hist-KL) metric and mean squared error (MSE). Results: Pix2pix demonstrated the best performance both quantitatively and qualitatively with mean PSNR, SSIM, and MSE metrics of 23.41 dB, 0.8, 0.004, respectively for MD generation, and 24.05 dB, 0.78, 0.004, respectively for FA generation. The new histogram similarity metric demonstrated sensitivity to differences in fine details between generated and real images with mean pix2pix MD and FA Hist-KL metrics of 11.73 and 3.74, respectively. Detailed analysis of clinically relevant regions of white matter (WM) and gray matter (GM) in the pix2pix images also showed strong significant (p < 0.001) correlations between real and synthetic FA values in both tissue types (R = 0.714 for GM, R = 0.877 for WM). Discussion/conclusion: Our results show that pix2pix's FA and MD models had significantly better structural similarity of tissue structures and fine details than other models, including WM tracts and CSF spaces, between real and generated images. Regional analysis of synthetic volumes showed that synthetic DWI images can not only be used to supplement clinical datasets, but demonstrates potential utility in bypassing or correcting registration in data pre-processing.

A Cancer Care Ontario Consensus-Based Organizational Guideline for the Planning and Delivery of Spine Stereotactic Body Radiation Therapy Treatment in Ontario.

The proposed recommendations are primarily based on the consensus opinion and in-field experience of the Ontario Health/Cancer Care Ontario stereotactic body radiation therapy (SBRT) for Spine Metastasis Guideline Development Group and published literature when available. Primary consideration was given to the perceived benefits for patients and the small likelihood of harm arising from recommendation implementation. Apart from the magnetic resonance imaging (MRI) follow-up strategy, all evidence was considered indirect and was provided by the working group in conjunction with their collective expertise in the field of SBRT. The application of an SBRT program requires a multidisciplinary team consisting of a radiation oncologist, spine surgeon, neuroradiologist, medical physicist, medical dosimetrist, and radiation therapist. In Canada, linear accelerators are the most used treatment delivery units and should follow technology-specific quality assurance procedures. Immobilization technique is location dependant. Treatment planning MRI sequences should be acquired no more than 14 days from the date of treatment. In the case of epidural disease, simulation MRI should be completed no more than 7 days from the date of treatment. After treatment, patients should be followed with routine clinical visits every 3 months for the first year, every 3 to 6 months during years 2 and 3, and every 4 to 6 months thereafter. The recommendations enclosed provide a framework for the minimum requirements for a cancer center in Ontario, Canada to offer SBRT for spine metastases.